DESCRIPTION (Verbatim from Applicant's Abstract): The objective of this project is to understand more fully the fundamental physics of ultrasound contrast agents CAs]. Many UCA microbubbles are now under development. They are composed of a variety of stabilizing shell materials and gases or gas mixtures. These components influence the dynamic response of the bubbles to time-varying acoustic pressures and thus the means by which they provide sonographic contrast and potentiate cavitation-related bioeffects. Numerous medical applications for UCAs have been described. However, the influence of UCA components on bubble dynamics is still not well understood and has not yet been explored systematically. The long-term objective of this project is to obtain through experimental measurements the fundamental physical and acoustical properties of commercial UCAs, both individually and in clouds, and to use these measurements to validate a broad theoretical model. These advances would: (1) permit improvement of existing contrast-based ultrasonic imaging, (2) provide a means for development of drug-encapsulated microbubbles that can be "programmed for fragility, thus permitting targeted delivery of chemicals to tissues via externally applied ultrasound, and (3) evaluate the potential of these agents to facilitate cavitation-related mechanical bioeffects, with emphasis on correlating quantitative changes in bubble dynamics to corresponding changes in "bioeffectiveness. We have performed a number of feasibility studies, using a variety of experimental techniques and UCAs to show how these goals could be realized. We propose to: (1) measure the dynamic response of individual UCA microbubbles by adapting a light scattering system used to study single bubble sonoluminescence; (2) use a high speed camera (2 x 107 frames/s), to visualize the sphericity and the collapse of UCAs; (3) develop improved theoretical models based on the Gilmore equation to simulate UCA behavior; (4) measure the acoustic parameters and pressure thresholds associated with disappearance of echo-contrast and inception of inertial cavitation in UCA clouds; (5) use custom-made UCAs with different shell thicknesses, sizes, degrees of agglomeration, and gas compositions; (6) use a high-end ultrasound imaging system to tune and create new pulsing schemes based on the acoustic response of each type of UCA; and (7) use a well-established bioassay (hemolysis of 40 percent hematocrit human erythrocytes in vitro) to correlate the type of bubble response with the amount of UCA induced bioeffect. Successful completion of this project will lead to significant advances in both diagnostic and therapeutic ultrasound applications.